Neuroendocrine Tumors Disease Background

Introduction

Neuroendocrine tumors (NETs) are rare, small, slow-growing epithelial neoplasms with predominant neuroendocrine differentiation found in most organs of the body and arise from cells throughout the diffuse endocrine system. Carcinoid tumors and pancreatic NETs are the most common. Carcinoid tumors arise from the lungs, gastrointestinal tract (ie stomach, small intestine, appendix, rectum) and thymus.

Epidemiology

There is an increased incidence of neuroendocrine tumors seen in Western countries compared to Asian and European countries. This observation may be due to underlying biologic factors, environmental factors, and health care patterns.  

Neuroendocrine tumors are present between the ages of 50-60 years old. Female individuals have a higher incidence in ages <65 years, while incidence is higher in male individuals in ages >65 years.  Incidence rates are highest among Black male individuals for rectal NETs and lung NETs in white individuals. Rectum is the most common site for NETs seen in Asian countries such as Japan, China, and Korea. 

Pathophysiology

Neuroendocrine tumors have cytologic features of an endodermal origin.  NETs have the ability to store and secrete various peptides and neuroamines. Some of these substances can cause specific clinical syndromes, while other substances may produce elevated plasma or urine levels that are not associated with a specific symptom complex or syndrome.

Risk Factors

The risk factors of neuroendocrine tumors are as follows: 

• Age
• Sex
• Family history of cancer
• Diabetes mellitus
• Gallbladder disease
• Obesity
• Pernicious anemia
• Smoking and alcohol consumption

Classification

The most common subtypes of pancreatic neuroendocrine tumors are:

• Insulinomas that produce insulin
• Gastrinomas, which produce gastrin, a hormone that helps digest food
• Glucagonomas that produce glucagon, a hormone that helps to raise blood sugar levels
• VIPomas produce vasoactive intestinal peptide (VIP) that helps digestion and a number of other body processes
• Somatostatinomas produce somatostatin, which helps with digestion

Less common neuroendocrine tumors arise in the parathyroid glands, adrenal glands, pituitary gland and calcitonin-producing cells of the thyroid gland.  

Majority of NETs are sporadic with poorly understood risk factors, but some are associated with inherited genetic syndromes such as multiple endocrine neoplasia (MEN), Von-Hippel Lindau (VHL) disease, tuberous sclerosis complex, and neurofibromatosis. Sporadic NETs can be clinically classified as functional if symptoms attributed to hormonal hypersecretion are present and non-functional if without any symptoms.